ESPEN Congress Geneva 2014 DISEASES ACROSS BORDERS: THE CASE OF IRRITABLE BOWEL SYNDROME

Transcription

1 ESPEN Congress Geneva 2014 DISEASES ACROSS BORDERS: THE CASE OF IRRITABLE BOWEL SYNDROME Fibre in gastroenterology: is there anything new to say? A. Forbes (UK)

2 Fibre in Gastroenterology Is there anything new to say? Alastair Forbes Norwich Medical School

3 Cocoa Theobroma cacoa Drink of Gods (Xocoatl) theo = God broma = drink Mexico (Maya, Incas, Aztecs) Aphrodisiac

4 Norwich

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6 Fibre an introduction Resistant carbohydrate Not digested by human enzymes Poorly absorbed Poorly metabolised 2 main groups

7 Fibre an introduction Polysaccharides with alpha (1,4) glycosidic bonds can be digested by the small intestine Polysaccharides with beta (1,4) glycosidic bonds cannot

8 Fibre an introduction Predominantly non-starch polysaccharides Also oligosaccharides and lignin (polyphenols) Mostly have structural roles in plants

9 Specific fibres some examples Cellulose beta (1,4) glucopyranoside Hemicelluloses various sugar monomers Pectin galacturonate & some rhamnose Mucilage plant gums Lignin highly branched phenylpropanoid units Oligosaccharides various monomer units Inulin beta (2,1) linked fructose polymer Resistant starch functional definition

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11 Fibre an introduction Insoluble and soluble fibre Physical and metabolic differences Water-holding capacity Viscosity Solubility Fermentability Prebiotic capacity Binding capacity

12 Fibre an introduction Dietary fibre properties also affected by Ripeness of food (eg fruit) Preparation raw vs cooked whole vs grated etc 10

13 Fibre water-holding Determined by physicochemical properties Higher in non-soluble fibre Effect on stool mass Influenced also by effects on flora as bacteria contribute to stool water content

14 Fibre solubility/viscosity Water-solubility affects proportion that reaches colon in health Some fibres form gels (eg pectin, guar) Viscous gels important in delaying absorption Lower the glycaemic and hypercholesterolaemic effects of foods

15 Fibre fementability Property mainly of soluble fibre Essential for colonic health Only source of essential short chain fatty acids

16 Fibre fermentability Saccharolytic fermentation dominates and especially so in proximal colon Proteolytic fermentation more distal (when most fermentable substrates exhausted) Putrefaction (anaerobic metabolism of peptides) also occurs yielding SCFAs and ammonia, thiols, indoles, etc

17 Fibre fermentability Saccharolytic fermentation mainly yields SCFAs, lactate, H 2 and CO 2 Butyrate 15% Propionate 25% Acetate 60% All are rapidly absorbed Provide ~5% of energy needs in health

18 Fibre SCFAs ~5% of energy needs in health Main energy source for colonocytes Promote absorption of salt and water Stimulate mucosal proliferation Increase mucus production mucosal blood flow & oxygen uptake Maintain mucosal integrity

19 Butyrate Most important and most active SCFA Increases MUC2 and mucus production Promotes cell differentiation Decreases paracellular permeability Enhances ICAM-1, enteroglucagon Direct anti-inflammatory effects TNFα, IL6, IL8, IFNγ, COX-2, NFκB

20 Fibre is anabolic? RCT of whole grain fibre End-point = urinary markers of protein catabolism Short-term study but impressive results Potential clinical value? Ross 2013

21 Prebiotic effects of fibre Concept parallel to probiotic Specific non-digestible carbohydrates growth of bacteria with health benefits Highest butyrate production is from fructose oligosaccharide and inulin pathogenic G+ve and G-ve bacteria Major effects on Clostridium, Lactobacilli and Bifidobacteria Clinical data largely supportive

22 Absorptive and binding effects of fibre Fibre is ion binding Historically thought to pose risk of inhibition of absorption of key minerals Recent evidence suggests the opposite Calcium uptake and BMD increased by fibre in adolescents Binding of bile salts and some bacteria may be valuable 20

23 Fibre and satiety/appetite control Delays gastric emptying Increases viscosity of gastric content Probable hormonal effects in small bowel Fruit, fibre foods and supplements reduce appetite in the short-term Visholm 2014 Meta-analysis confirms (minor) weight loss Camilleri 2010

24 Viscous fibre and glycaemia Benefit from delayed gastric emptying Slower small bowel transit Less glucose transport through unstirred layer Reduced access of amylase to dietary starch Lower postprandial glucose level ( AUC)

25 Viscous fibre and glycaemia In combination reduce post-prandial glucose and increase insulin sensitivity Especially guar, pectin, β-glucan Improve diabetic control Probably non-fermentable fibre reduces risk of diabetes eg Fujii 2013, Yu 2014

26 Viscous fibre and blood lipids Lowers LDL (no effect on other lipids) No effects from non-soluble fibre Attributed in part to effect on bile salts Small effect Bigger overall influence on CVS morbidity from insoluble fibre but mechanisms remain unclear

27 Fibre and the gut Transit normalised if abnormal Frequency increased by 1.4x per week if constipation Mainly bulk/water effect from insoluble fibre Diarrhoea ameliorated and duration shortened (acute in children & antibioticassociated) Enteral tube feed-associated diarrhoea improved Elia 2008

28 Fibre and IBS Dietary guidance & evaluation in IBS: n=46 Review at 3-6 months Advice was not just increased fibre Patients increased dairy and vitamin intakes with decrease in FODMAPs Overall symptom score and QoL improved No correlation with any food group! Mazzawi 2013

29 Fibre and IBS Systematic review and meta-analysis Comparisons with placebo, control or usual management; n = 906 Significant overall benefit: RR = 0.86 CI ; NNT =10 Effect from soluble fibre: RR = 0.83 No significant effect from bran: RR = 0.9 Unclear if effect limited to IBS subgroups Moayyedi 2014 Epub

30 Fibre and diverticula Common and responsible for considerable morbidity from complicaions Because of low fibre Western diet

31 Fibre and diverticula Common and responsible for considerable morbidity from complications Not because of low fibre Western diet No protection against diverticulosis Association with diverticulitis also questioned Risk from seeds/nuts once diverticulosis present also not supported by data Peery 2013

32 Fibre and inflammation Relatively few reliable human data Animal models show benefit in several forms of colitis Butyrate probably effective in human colitis Plantago ovata not helpful in preventing relapse of ulcerative colitis Hallert 2003, Vernia 2003, Fernandez-Banares

33 Fibre and IBD New prospective study in IBD pathogenesis Nurses Health Study n=170, incident CD, 338 UC compared to mean

34 New prospective study in IBD pathogenesis Nurses Health Study n=170, incident CD, 338 UC compared to mean Intake of highest quintile of fibre (24.3g/d) associated with 40% reduction in risk of CD HR 0.59: CI Most of benefit from fruit fibre Little influence of fibre on UC incidence HR 0.82 (NS) Fibre and IBD Ananthakrishnan 2013

35 Fibre and colon cancer Not relevant after diagnosis Evidence for protection from cereal fibre still controversial. No benefit from insoluble dietary fibre (FDA 2000) Clear benefit from all fibre (EPIC 2003)

36 Fibre and colon cancer Confusion perhaps because of typical difficulties of interpreting diet in aetiology Or other factors?

37 Fibre and colon cancer Confusion perhaps because of typical difficulties of interpreting diet in aetiology Or other factors? Difference between dietary and supplementary fibre Host genome Dietary co-factors

38 Fibre and colon cancer Type of fibre - EPIC database Plasma alkyl resorcinol reflects wholegrain intake (wheat and rye) Higher in North European populations than Mediterranean Unclear how to interpret Kyro 2014

39 Fibre and colon cancer Calcium also important thought to be protective - but possibly a fibre effect Case-control study of 1556 (703 vs 853) incident cases using 148-item Food Frequency Questionnaire Higher consumption of calcium associated with lower colon cancer risk OR = 0.93 (CI: ) for every extra 100 mg Ca/day Galas 2013

40 Fibre and colon cancer >1000 mg/day yielded OR of 0.54 CI: Effect modified by dietary fibre Cancer risk reduced with increasing levels of dietary calcium and fibre intake to more than additive extent Galas 2013

41 Fibre and colonic adenomas Meta-analysis of almost patients Summary relative risk of high vs low fibre intake = 0.72 (CI ) Stronger effect in case-control than in cohort studies (RR 0.66 vs 0.92) Effect strongest for cereal fibre and least for vegetable fibre Ben 2014

42 Fibre in HNPCC / Lynch Interventional study of family members Supplementary fibre No apparent effect on cancer risk Mathers

43 Fibre and colon cancer Genome-wide diet-gene interactions Diet and ~2.7m genetic variants studied in >9000 cases and >9000 controls Red and processed meat intake more common in cases; fruit / vegetable / fibre less

44 Fibre and colon cancer Genome-wide diet-gene interactions Diet and ~2.7m genetic variants studied in >9000 cases and >9000 controls Red and processed meat intake more common in cases; fruit / vegetable / fibre less 2 specific polymorphisms of rs (on 10p) (TG and TT) plus dietary processed meat yield OR of 1.3 and 1.4 But GG genotype has no link OR 1.03 Figueiredo 2014

45 Fibre also implicated in gastric cancer Meta-analysis of >580,000 cases Highest vs lowest fibre intakes compared Retrospective and much heterogeneity Overall protective effect OR 0.58 Different types of fibre not analysable Equivalent to a 44% reduction in risk for a 10g/d dietary supplementation Zhang 2013

46 Fibre also implicated in pancreatic cancer Dietary analyses in case-control study of 326 vs 652 controls 4 dietary patterns identified Those with the fibre and vitamin diet had the lowest rate of pancreatic cancer OR 0.55 (CI ) While the red meat diet doubles the risk Bosetti 2013

47 Fibre in artificial feeding Historically, commercially prepared feeds were without fibre and the addition of fibre was special Increasingly fibre-containing feeds are considered the default typically 5-10g/L Is this correct and safe?

48 Fibre in artificial feeding Indicated if constipation or diarrhoea Confirmation of value is stronger for patients with diarrhoea than it is for patients with constipation Rabenek 1997

49 Fibre in artificial feeding Contra-indicated in some GI conditions Intestinal strictures questionable Abdominal compartment syndrome but enteral feeding contra-indicated too Acute pancreatitis? (Besselink 2008) Gastroparesis? Short bowel syndrome? Poor appetite?? No evidence against in most conditions

50 Fibre what next? Clear recommendations for boosting fibre intake in the general population Benefits of certain or probable extent GI health, CVS, diabetes, cancer, etc Soluble and insoluble fibres yield complementary actions No evidence for harm Should be default for artificial feeding

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